Tayefeh Sascha, Kloss Thomas, Kreim Michael, Gebhardt Manuela, Baumeister Dirk, Hertel Brigitte, Richter Christian, Schwalbe Harald, Moroni Anna, Thiel Gerhard, Kast Stefan M
Eduard Zintl-Institut für Anorganische und Physikalische Chemie, Technische Universität Darmstadt, Darmstadt, Germany.
Biophys J. 2009 Jan;96(2):485-98. doi: 10.1016/j.bpj.2008.09.050.
A computational model for the open state of the short viral Kcv potassium channel was created and tested based on homology modeling and extensive molecular-dynamics simulation in a membrane environment. Particular attention was paid to the structure of the highly flexible N-terminal region and to the protonation state of membrane-exposed lysine residues. Data from various experimental sources, NMR spectroscopy, and electrophysiology, as well as results from three-dimensional reference interaction site model integral equation theory were taken into account to select the most reasonable model among possible variants. The final model exhibits spontaneous ion transitions across the complete pore, with and without application of an external field. The nonequilibrium transport events could be induced reproducibly without abnormally large driving potential and without the need to place ions artificially at certain key positions along the transition path. The transport mechanism through the filter region corresponds to the classic view of single-file motion, which in our case is coupled to frequent exchange of ions between the innermost filter position and the cavity.
基于同源建模和在膜环境中的广泛分子动力学模拟，创建并测试了短病毒Kcv钾通道开放状态的计算模型。特别关注了高度灵活的N端区域的结构以及膜暴露赖氨酸残基的质子化状态。考虑了来自各种实验来源的数据、核磁共振光谱和电生理学数据，以及三维参考相互作用位点模型积分方程理论的结果，以便在可能的变体中选择最合理的模型。最终模型显示，无论是否施加外部电场，离子都能在整个孔中自发跃迁。非平衡传输事件可以在没有异常大的驱动电位且无需在跃迁路径上的某些关键位置人为放置离子的情况下可重复地诱导产生。通过滤器区域的传输机制符合单通道运动的经典观点，在我们的案例中，这与最内层滤器位置和腔之间离子的频繁交换相关联。
